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Epidemiology studies show that consumption of certain naturally occurring chemicals (generally plant-derived) can protect against the development of cancer (chemoprevention).Resveratrol, a phytoalexin found in foods such as grapes and wine as a glucoside , is one such chemical. Our group has previously shown that treating mammalian cells with resveratrol aglycone can reduce the mutagenicity of the cooked meat-derived carcinogens 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP). However, the anti-mutagenic effect of resveratrol in vivo has not been previously reported. In this study, daily treatment of resveratrol up to 1000µg/kg for 10 days was well tolerated in Muta TM Mouse mice. Treating Muta TM Mouse mice with the meat carcinogen 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine induced mutation in the colon. Co-treatment of resveratrol and PhIP reduced the mutation frequency induced by PhIP in the colon by about 25% in a treatment group of mixed male and females. Analysing males and females separately revealed a sex difference in the response to PhIP and to the effect of resveratrol on PhIP-induced mutagenicity. In males compared to females, PhIP was a more potent colonic mutagen and resveratrol was more effective at attenuating the mutagenic response ( ~35% in males but only 9% in females). The reason for this sex difference in both PhIP mutagenicity and response to resveratrol is not clear. However, resveratrol treatment was also shown to powerfully inhibit ethoxyresorufin-O-deethylase activity in vivo, indicating that the antimutagenic affects are likely linked to metabolic activation of PhIP.These data suggest that resveratrol has anti-mutagenic effects in vivo, supporting its potential to act as a chemopreventative.

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